SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus) has constantly been evolving into different forms throughout its spread in the population. Emerging SARS-CoV-2 variants, predominantly the variants of concern (VOCs), could have an impact on the virus spread, pathogenicity, and diagnosis. The recently emerged "Omicron" variant has exhibited rapid transmission and divergence. The spike protein of SARS-CoV-2 has consistently been appearing as the mutational hotspot of all these VOCs. In order to determine a deeper understanding of the recently emerged and extremely divergent "Omicron", a study of amino acid usage patterns and their substitution patterns was performed and compared with those of the other four successful variants of concern ("Alpha", "Beta", "Gamma", and "Delta"). We observed that the amino acid usage of "Omicron" has a distinct pattern that distinguishes it from other VOCs and is significantly correlated with the increased hydrophobicity in spike proteins. We observed an increase in the non-synonymous substitution rate compared with the other four VOCs. Considering the phylogenetic relationship, we hypothesized about the functional interdependence between recombination and the mutation rate that might have resulted in a shift in the optimum of the mutation rate for the evolution of the "Omicron" variant. The results suggest that for improved disease prevention and control, more attention should be given to the significant genetic differentiation and diversity of newly emerging variants.
Keywords: SARS-CoV-2; VOC; amino acid usage; mutation rate; receptor binding domain; recombination.